Drug Interaction Report

MONITOR: Tricyclic antidepressants may increase serum phenytoin levels. In vitro studies suggest the mechanism may involve inhibition of CYP450 2C19-catalyzed phenytoin p-hydroxylation by tricyclic antidepressants, especially imipramine and amitriptyline. Phenytoin may induce the hepatic metabolism of desipramine resulting in decreased plasma concentrations. In addition, tricyclic antidepressants may lower the seizure threshold.

MANAGEMENT: Clinical monitoring of patient response, tolerance, and serum phenytoin concentrations is recommended. Patients should be advised to notify their doctor if they experience loss of seizure control or symptoms of phenytoin toxicity (drowsiness, visual disturbances, change in mental status, nausea, or ataxia). Phenytoin dosage may need to be adjusted.

GENERALLY AVOID: Concomitant use of ethanol and a tricyclic antidepressant (TCA) may result altered TCA plasma levels and efficacy, and additive impairment of motor skills, especially driving skills. Acute ethanol ingestion may inhibit TCA metabolism, while chronic ingestion of large amounts of ethanol may induce hepatic TCA metabolism.

MANAGEMENT: Patients should be advised to avoid alcohol during TCA therapy. Alcoholics who have undergone detoxification should be monitored for decreased TCA efficacy. Dosage adjustments may be required.